The objective of this research is to investigate the mechanism of control of contraction in striated muscle in both the normal and diseased states at the cellular and molecular level. A major mechanism of control is through excitability of the cell membrane regulating the intracellular Ca concentration, but there are other factors such as (Mg), (MgATP), pH, etc. which can vary a relationship between tension and Ca concentration. In addition to these chemical factors, there are mechanical factors such as sarcomere length and muscle shortening which are important. The effects of these various factors on control of contraction will be investigated. This work involves three areas of research. One is how these chemical factors modify the Ca sensitivity and contraction of the system. The second involves how mechanical factors such as muscle length affect the Ca release process and contractile properties. The third involves an investigation of the cause of paralysis in insulin-treated muscles from potassium-deficient rats. BIBLIOGRAPHIC REFERENCES: Kao, I. and Gordon, A.M. Mechanism of insulin-induced paralysis of muscles from potassium-depleted rats. Science 188:740-741 (1975). Ridgway, E.B. and Gordon, A.M. Muscle activation: Effects of small length changes on calcium release in single fibers. Science 189:881-884 (1975).